How Do Antianxiety Agents Work?

Antianxiety agents are medications prescribed to treat anxiety and related disorders. Antianxiety agents work on the central nervous system to reduce hyperactivity in the brain and induce a calming effect. Many of the antianxiety agents are also used for sedation, as muscle relaxants and to prevent seizures.

Antianxiety medications are of two main types:

Benzodiazepines

Benzodiazepines work on the brain’s limbic system, which regulates emotional and behavioral responses, and reticular formation which regulates sleep and consciousness. Benzodiazepines increase the activity of gamma-aminobutyric acid (GABA), a chemical messenger (neurotransmitter) in the brain that inhibits nerve signals.

Benzodiazepines bind to GABA receptors, a type of protein molecules on the membranes of nerve cells (neurons), and increase the inflow of chloride ions, which enhances GABA’s effects. GABA inhibits electrical activity in the brain and produces a sedative effect.

Nonbenzodiazepines

Currently, two nonbenzodiazepines are used as antianxiety agents:

• Buspirone: Buspirone increases the level of serotonin, a neurotransmitter that has many functions including mood regulation. It is not fully clear how buspirone reduces anxiety, but the effect is thought to be from increased serotonin activity in the anxiety/fear circuitry of the brain. Buspirone does not affect GABA receptors, hence does not produce sedation.
• Meprobamate: Meprobamate works on GABA receptors and has mild sedative, muscle relaxing, and anticonvulsant effects.

Antianxiety agents may be administered through many routes such as:

• Oral: Tablets, capsules, solutions, and syrups
• Injections:
  • Intravenous (IV): Injected into the vein
  • Intramuscular (IM): Injected into the muscle
• Rectal: Gel applied inside the rectum

Antianxiety medications are chosen based on specific patient needs and conditions. Antianxiety agents are used in the treatment of conditions which include the following:

FDA-Approved

• Anxiety
• Anxiety disorders
• Panic disorder
• Anxiety associated with depression
• Preoperative apprehension and anxiety
• Seizure disorders
• Acute alcohol withdrawal
• Endoscopy
• Preoperative sedation and anterograde amnesia (short-term loss of memory)
• Anesthesia induction and maintenance
• Sedation of intubated/ventilated patients
• Sedation in the ICU
• Muscle spasm
• Insomnia (short-term treatment)
• Status epilepticus (a medical emergency, when a seizure lasts longer than five minutes)

Orphan designation:

• Hyperekplexia (a rare hereditary neurological disorder that causes excessive startle reaction to sudden noise or touch)
• Recurrent, acute, repetitive seizures
• Repetitive seizures caused by Dravet syndrome, a rare type of epilepsy
• Organophosphorus poisoning (exposure to a neurotoxic substance that can cause muscle weakness, cramps, and paralysis)

Off-label uses:

• Premenstrual syndrome
• Essential tremor
• REM sleep behavior disorder
• Burning mouth syndrome
• Tardive dyskinesia (a neurological disorder that causes involuntary repetitive movements)
• Chronic insomnia
• Chemotherapy-induced nausea and vomiting
• Smoking cessation
• Generalized anxiety disorder

Side effects of antianxiety agents may include the following:

• Somnolence (drowsiness)
• Headache
• Lightheadedness
• Constipation
• Diarrhea
• Nausea
• Vomiting
• Increased or decreased appetite
• Weight change
• Xerostomia (dry mouth)
• Nasal congestion
• Asthenia (weakness)
• Fatigue
• Depression
• Sedation
• Memory impairment
• Irritability
• Cognitive disorders
• Insomnia
• Confusion
• Disorientation
• Nervousness
• Akathisia (restlessness)
• Euphoria
• Delirium
• Dream disturbances
• Mania and hypomania
• Excessive talkativeness
• Disinhibition
• Suicidal ideation/attempt
• Paradoxical reactions such as:
  • Anxiety
  • Excitation and agitation
  • Anger, hostility, and aggression
• Muscle weakness
• Muscle cramps and pain
• Dystonia (involuntary muscle contractions)
• Rigidity
• Numbness
• Paresthesia (prickling sensation)
• Ataxia (impaired coordination)
• Unsteadiness
• Vertigo
• Tremor
• Convulsions/seizures
• Worsening of tonic-clonic seizures
• Accidental falls, injuries, and fractures
• Dysarthria (speech disorder, slurred speech)
• Tinnitus (ringing in the ears)
• Visual disturbances
• Blurred vision
• Diplopia (double vision)
• Eye accommodation (focusing) disorder 
• Increased ocular pressure
• Nystagmus (involuntary eye movement)
• Photophobia (light sensitivity)
• Decreased or increased salivation
• Apnea (cessation of breathing)
• Sleep apnea
• Decreased respiratory rate
• Respiratory depression
• Oxygen desaturation
• Upper respiratory infection
• Coughing
• Sore throat
• Nonspecific chest pain
• Hiccups
• Rhinitis (inflammation of the nasal passage)
• Difficult micturition (urination)
• Urinary retention
• Urinary incontinence
• Urinary frequency
• Rectal bleeding
• Tachycardia (rapid heartbeat)
• Palpitations
• Hypotension (low blood pressure)
• Heart failure
• Abnormal ECG
• Syncope (fainting)
• Blood dyscrasias (disorders)
• Neutropenia (low blood count of neutrophils, a type of immune cells)
• Agranulocytosis (low granulocytes, immune cells with granules)
• Aplastic anemia (anemia due to reduced red cell production)
• Bruising
• Local effects from IV administration such as:
  • Pain and swelling
  • Phlebitis (inflammation of veins)
  • Thrombophlebitis (phlebitis with a blood clot in a vein)
  • Carpal tunnel syndrome
  • Tissue necrosis
• Hypersensitive reactions such as:
  • Rash
  • Urticaria (hives)
  • Maculopapular eruption (flat lesions with raised bumps)
  • Bullous dermatosis (skin disease with blisters)
  • Dermatitis
  • Angioedema (swelling in the tissue under the skin or mucous membranes)
  • Peripheral edema
  • Anaphylaxis (severe allergic reaction)
  • Stevens-Johnson syndrome (a rare medical emergency with flu-like symptoms and a painful rash)
• Alopecia (hair loss)
• Eosinophilia
• Liver enzyme elevation
• Hepatitis
• Jaundice
• Liver failure
• Menstrual irregularities
• Menstrual disorders
• Increase or decrease in libido
• Sexual dysfunction
• Impotence
• Hyperprolactinemia (high prolactin levels in the blood, which can induce abnormal breast milk production and other hormonal disorders)
• Galactorrhea (abnormal milk production and leakage)
• Gynecomastia (breast tissue development in males)

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of antianxiety drugs include:

• alprazolam
• Ativan
• buspirone
• chlordiazepoxide
• clonazepam
• clorazepate
• Diastat
• Diastat AcuDial
• diazepam
• Klonopin
• Librium
• lorazepam
• meprobamate
• midazolam
• oxazepam
• Seizalam
• Tranxene SD
• Tranxene T-Tab
• Valium
• Xanax
• Xanax XR